Suppository has a number of advantages. It not only can avoid decomposition of drugs by acid or enzyme in gastrointestinal tract when the drugs are orally administered or can avoid irritation stimulation to gastrointestinal mucosa which is caused by direct contact of drugs with mucosa, but also is physiologically less affected by such factors as variations of pH in gastrointestinal tract, the gastric empty rate, mobility of gastrointestinal tract, mutual actions between food components, and the like. In addition, suppository is safer and easier to administer than injection. Thus, it is a form of preparation which is applicable even to infant or elderly patients.
A number of incidents, however, have been reported on side effects of suppositories due to a rapid increase in blood concentration of drugs. On the other hand, drugs which are rapidly eliminated from blood must be administered more frequently in order to maintain their effect for a longer period of time. Administrating several times a day not only gives pain to the patients, but also is undesirable from the pharmacological aspect, e.g., irritation to mucosa, etc.
Development of a sustained-release suppository preparation which can avoid a rapid increase in blood concentration of drugs and exhibit its action for a longer period of time has therefore been desired.
In view of this situation, the present inventors have undertaken extensive studies and found that the release rate of acidic drugs or salts thereof, which can be absorbed by rectal administration and satisfactorily exhibit their effects, can be retarded if they are formulated together with an acidic compound or a pH buffering agent, thus controlling a rapid increase in blood concentration immediately after the administration and maintaining the blood concentration of the drug for a long period of time. This finding has led to the completion of the present invention.